The purpose of this study is to test how safe and effective the combination of RAD001 and
erlotinib is in patients with neuroendocrine tumors.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- ≥1 measurable disease site per RECIST, not previously irradiated (if previous
radiation to marker lesion(s), need evidence of PD)
- Histologic dx of well- to moderately-differentiated NET: low- or intermediate-grade,
islet cell carcinoma, pancreatic NET, carcinoid, atypical carcinoid, paraganglioma,
pheochromocytoma. No longer enrolling carcinoid patients as of 4/25/2011.
- ≥4 wks since completion of prior investigational drug tx or other tx(radiation,
chemotherapy, immunotherapy, antibody-based tx); recovery from acute toxicities of
prior tx
- ECOG ≤2
- ANC ≥1500/μL
- Plts ≥100,000/μL
- Hgb >9 gm/dL
- Total bilirubin ≤2. 0 mg/dL or 1. 5XULN
- Serum transaminases ≤2. 5xULN (≤5xULN if liver mets)
- Serum Cr ≤2. 0 mg/dL or 1. 5XULN
- Fasting serum glucose <150 mg/dL or <1. 5xULN
- Fasting serum cholesterol ≤300 mg/dL OR ≤7. 75 mmol/L AND fasting triglycerides
≤2. 5xULN
- INR ≤1. 5
- Written informed consent, compliance w/study requirements
- Archived tissue if available
- Negative urine/serum pregnancy test w/in 7 days prior to Day 1
Exclusion Criteria:
- Poorly differentiated NET, high-grade NET, adenocarcinoid, goblet cell carcinoid,
small cell carcinoma
- Major surgery or traumatic injury w/in 4 wks, inadequate recovery from side effects
of any surgery, or likely to require major surgery during study
- Liver-directed therapy w/in 2 mths of enrollment. Prior tx w/ radiotherapy (including
radiolabeled spheres, cyberknife, hepatic arterial embolization (w/ or w/o
chemotherapy), cryotherapy/ablation) allowed if areas of measurable disease being
used for the study are not affected, or if PD can clearly be documented in the area
- Prior tx w/ EGFR inhibitor or mTOR inhibitor
- Known hypersensitivity to RAD001 or other rapamycins
- Chronic, systemic tx w/ corticosteroids or another immunosuppressive agent (topical
or inhaled corticosteroids are allowed)
- Immunization w/ attenuated live vaccines w/in 1 wk of study entry or during study
- Uncontrolled brain or leptomeningeal mets, including pts who continue to require
glucocorticoids for brain or leptomeningeal mets
- Other malignancies w/in the past 3 years except for adequately treated carcinoma of
the cervix, basal/squamous cell skin carcinomas, or other in situ cancer
- Severe and/or uncontrolled intercurrent medical conditions or other conditions that
may affect study participation, including, but not limited to:
- Severely impaired lung function (spirometry and DLCO that is 50% of the normal
predicted value and/or O2 saturation ≤88% at rest on room air)
- Symptomatic congestive heart failure (CHF) of NYHA Class III or IV
- Unstable angina pectoris, symptomatic CHF, myocardial infarction w/in 6 mths of Day
1, uncontrolled cardiac arrhythmia or any other significant cardiac disease
- Uncontrolled diabetes (fasting serum glucose ≥ 150 mg/dL or >1. 5xULN)
- Any active (acute or chronic) or severe infection, disorder, or nonmalignant medical
illness that is uncontrolled or whose control may be jeopardized by study tx
- Liver disease
- Hx of HIV seropositivity or other immunocompromised state
- GI function impairment or disease that may alter absorption of RAD001 or erlotinib
- Active, bleeding diathesis or on oral anti-vitamin K medication (pts needing
anticoagulation must use LMW heparin)
- Hx of other disease, metabolic dysfunction, or physical exam or lab finding giving
reasonable suspicion of disease/condition that contraindicates study tx, might affect
study results or puts the pt at high risk
- Pregnant or breast feeding females
- Adults of reproductive potential not willing to use effective methods of birth
control during tx and ≥8 wks after completing tx
- Inability to comply w/ objectives and procedures
- Inability to comply w/ concomitant medication restrictions